Thursday, August 05, 2004

What Do We Know: A study out today in the New England Journal of Medicine suggests that doctors may have been too hasty and careless in their adoption of a previous study regarding the treatment of heart failure. In 1999, the Journal published a study known by the too-cute acronym RALES (It stands for "Randomized Aldactone Evaluation Study", but "rales" is also the name for the sound we hear when we listen to lungs full of fluid from congestive heart failure), which suggested that the drug spironolactone is the better choice among diuretics for severe heart failure. But spironolactone has the side effect of raising potassium levels as do several other drugs commonly used for congestive heart failure. One of those other drugs is the class of drugs known as ACE inhibitors, a class which is also especially prone to raising potassium levels. Not surprisingly, using the two of them in combination has taken its toll :

The Canadian researchers examined whether the use of spironolactone had increased after the 1999 research, and what impact it was having on patients who take a standard ACE inhibitor and had been sick enough to be recently hospitalized. ACE inhibitors relax the blood vessels and lower blood pressure but can contribute to high potassium when combined with spironolactone.

The researchers tracked prescription and hospital records from 1994-2001 for about 1.3 million residents of the province of Ontario who were over 65.

``We found when the drug took off in mid-1999, so did rates of hospitalization for high potassium and deaths in hospital associated with that,'' said Juurlink.

Prescription rates for spironolactone increased fivefold, and hospitalizations and deaths from high potassium tripled. The number of heart patients hospitalized jumped from 4 to 11 per 1,000; deaths rose from 0.7 to 2 per 1,000.

In Ontario alone, researchers estimated that broader use of spironolactone resulted in 73 additional hospital deaths and 560 more hospitalizations in 2001 than would have been expected.

One of the RALES researchers told the AP:

``This reflects the lack of education of doctors, I think, and that's what worries me most,'' said Remme, director of the Sticares Cardiovascular Research Institute in the Netherlands.

What it may actually reflect is the overeducation of doctors. It's true that as a group we are often too quick to embrace treatment recommendations that come out in studies without considering the likely long-term consequences. The studies get quoted and promulgated via educational conferences and practice guidelines, and before you know it, they become the standard of care. Doctors don't like to buck the standard of care. It makes us look like we're behind the times or worse, stupid. So no one ever stops to question the wisdom of piling all of these new treatment recommendations onto one patient.

That's what has happened here. The ACE inhbitors are so strongly recommended for patients with heart failure, that their use has become a standard of quality against which physician performance is measured by insurance companies. Add to that the spironolactone and you have a recipe for disaster. What's even more alarming is that for some doctors, meeting those standards is more important than what's going on with the patient. The insurance companies will audit their charts for ACE inhibitor prescriptions, but not for hyperkalemia or other side effects. Case in point - one of my patients developed hyperkalemia as well as early signs that her kidneys were stressed while on an ACE inhibitor and spironolactone. I stopped them both, but her cardiologist told her to restart the ACE inhibitor. When I questioned him he said that he would rather she have a slighlty higher potassium level and mild renal insufficiency and stay on the ACE. He felt the benefits outweighed the side-effects. I thought he wanted his treatment record to look nice. I ended up admitting her for acute renal failure a week later, caused by her ACE inhibitor. Only then would he admit the drug wasn't a good choice for her.

The treatment of congestive heart failure is only one example in which the adoption of treatment guidelines are outstripping our knowledge of the consequences of that treatment. Diabetics are routinely on several different classes of medications to meet standards of care in everything from their blood sugar control to cholesterol to the functional capacity of their kidneys. And each of those medications has the potential to interact with one another. The more medications any one person takes, the more likely there will be drug interactions.

This used to be a cornerstone of good medical therapy - avoiding what we call polypharmacy. But in the past ten or so years, that cornerstone has been neglected as we rush to adopt the best and latest drug therapy to reduce every conceivable risk. No one has bothered to study whether or not we might be doing more harm by prescribing all those drugs to meet our guidelines. Until now. Let's hope this kind of study catches on.